This is a randomized trial for patients with brain metastases in the primary motor cortex who have not had seizures to receive either the prophylactic anti-seizure medication levetiracetam (also known by its trade name Keppra) or proceed with standard of care management, which does not currently include prophylactic levetiracetam. Patients who enroll to this trial will be randomized to receive prophylactic levetiracetam or not receive prophylactic levetiracetam.

Brain metastases (BrM) impact 10%-40% of patients with solid malignancies and are associated with significant clinical sequelae, including development of seizures. The development of seizures has the potential for significant detriment on patient quality of life. The goal of this study is to evaluate the role of levetiracetam as primary prophylaxis in seizure-naïve patients with metastases in primary motor cortex, an area at high risk of seizures. Patients will be randomized to receive levetiracetam/ASM or to receive no ASM therapy.

Inclusion Criteria:

1. Participants must have a biopsy proven solid malignancy with at least one intracranial lesion radiographically consistent with or pathologically proven to be a brain metastasis located in the primary motor cortex measuring 0.5 cm or larger in maximal unidimensional size
2. Age of at least 18 years
3. Karnofsky performance status of at least 60
4. Estimated survival of at least 3-6 months in the opinion of the enrolling clinician and/or study PI
5. Ability to understand and the willingness to sign a written informed consent document by either ink on paper or a DF/HCC approved eConsent medium

Exclusion Criteria:

1. Participants with prior seizures as this is a study for seizure naïve patients
2. Participants with an allergy to levetiracetam as levetiracetam is the prophylactic anti-seizure medication under study
3. Participants concurrently taking (i.e. at enrollment) an ASM for non-seizure indications at clinically relevant doses (gabapentin 1800 mg/day or higher, pregabalin 300 mg/ day or higher, lamotrigine 150 mg/ day or higher, valproic acid 1000 mg/ day or higher, topiramate 200 mg/ day or higher, carbamazepine 200 mg/ day or higher, oxcarbazepine 300 mg/ day or higher, primidone 100 mg/day or higher) because use of these medications could bias the study toward the null
4. Participants who cannot tolerate a magnetic resonance imaging (MRI) study of the brain, which is required to determine the presence of and follow the course of brain metastases under study
5. Participants who cannot receive gadolinium as MRI of the brain with contrast is required
6. Participants with end stage renal disease due to risk of nephrogenic systemic fibrosis in this patient population after exposure to gadolinium-based contrast agents
7. Participants with widespread, definitive leptomeningeal disease given that leptomeningeal disease and brain metastases are different entities
8. Pregnant women are excluded from this study because levetiracetam crosses the placenta. In addition, the potential deleterious effects of gadolinium on the developing fetus are not completely known
9. Women who are breastfeeding are excluded from this study because levetiracetam enters breast milk. In addition, the potential deleterious effects of gadolinium in breast milk remain unknown