Inclusion Criteria:

• Age ≥18 years
• Radiographic evidence or histopathologic confirmation of CNS malignancy, with or without prior resection. 
• Planned (cohort 1) or completed (cohort 2) fractionated brain radiation. The therapeutic brain radiation treatment volume should exceed 30 cubic cm, including the volume of brain tissue occupied by infiltrative disease. Volume occupied by solid non-infiltrative disease (e.g. meningioma, metastatic disease, cystic cavity, resection cavity), should be excluded from the estimated treatment volume.
• Provide written informed consent for the current study and the Neuro-oncology biorepository for archiving of CSF and blood samples collected on this protocol.
• Expected survival >6 months and Karnofsky performance status ≥60.
• Willing and able to adhere with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations.
• The following laboratory values obtained ≤14 days prior to registration:
• •           Alanine aminotransferase (ALT) and aspartate transaminase (AST) <3 x ULN (≤5 x ULN for patients with baseline liver disease).
• •           Serum creatinine ≤1.5 mg/dL.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Willingness to provide mandatory CSF and blood and able to undergo MRS/MRI with gadolinium.
• Male and female patients of childbearing potential must agree to use a dual method of contraception (a highly effective method of contraception in conjunction with barrier contraception) consistently and correctly from the first dose of study drug (Arm B only) until 90 days after the last dose of study drug.

Exclusion Criteria: 

• Uncontrolled and/or intercurrent illness which limits safety of or compliance to study proceedings.
• Vulnerable populations: pregnant or nursing women (Arm B exempt), prisoners, mentally handicapped.
• Patients with recurrent brain tumor after prior radiation.
• Cohort 1 only: History of prior brain radiation, with prior cumulative target radiation treatment volume exceeding 2 cubic centimeters.
• Patients who do not have an implanted CSF access device (who would thus require multiple LPs for participation) should be excluded if they have any contra-indication to lumbar puncture. This includes but is not limited to obstructive hydrocephalus or posterior fossa mass or cerebral edema that could increase the risk of brain herniation.
• Patients who do not have an implanted CSF device and are on anti-platelet therapy (other than Aspirin which is considered low risk) or anticoagulation (coumadin, Eliquis) must discontinue these prior to each lumbar puncture to participate. Patients unwilling or unable to safely do so should not be enrolled.
• Participants who are unable to swallow tablets or who are at risk for impaired absorption of oral medication. NOTE: This includes but not limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal resection.
• Patients with recent (<3mo) administration of, or known hypersensitivity or allergy to any active study drug currently available for randomization (initially oxaloacetate). 
• Current use of resveratrol, CoQ10 (coenzyme Q10), coconut oil/other medium chain triglyceride-containing (i.e. Axona) supplements, or curcumin will be excluded unless willing to discontinue them 14 days prior to the start of baseline visits and remain off for study duration.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/16/22. Questions regarding updates should be directed to the study team contact.