A Study of the Safety of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Subjects With Newly Diagnosed High Grade Glioma Receiving Standard of Care

Inclusion Criteria: 1. Subject has given written informed consent 2. Subject is at least 18 years old 3. Subjects must have presumed newly diagnosed high grade glioma prior to tissue diagnosis or definitive initial surgical resection 4. Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for planned resection of enhancing region of tumor OR for those subjects who are not candidates for resection, based on the pre-operative evaluation by neurosurgeon, the subject has a presumed newly diagnosed high grade glioma accessible by a technically feasible stereotactic trajectory 5. Laboratory values adequate for subject to undergo surgery, including: * Platelet count ≥ 100,000/mm3 * Hgb ≥ 10 g/dL * Absolute neutrophil count (ANC) ≥ 1,500/mm3 * Normal PT/PTT (subnormal PT/PTT acceptable) * Adequate liver function, including total bilirubin ≤ 1.5 x ULN (unless known Gilbert's syndrome); ALT ≤ 2.5 x ULN 6. The subject has a KPS ≥ 70 7. Women of childbearing potential (≥12 months of non-therapy-induced amenorrhea or surgically sterile) must have had a negative serum pregnancy test within the past 21 days and must use a birth control method in addition to barrier methods (condoms) 8. Subject or subject's partner is willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer 9. Subject has an absolute lymphocyte count (ALC) ≥ 500/mm3 10. Estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft Gault formula Exclusion Criteria: 1. History of other malignancy, unless the subject has been disease free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment 2. A contrast enhancing brain tumor that is any of the following: * Multi focal (defined as 2 separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid attenuated inversion recovery (FLAIR) or T2 sequences); * Associated with either diffuse subependymal or leptomeningeal dissemination; or \> 5 cm in any dimension * Location in the brainstem, cerebellum or spinal cord Expansion Cohort: OR For those subjects who are not candidates for resection, injection of the tumor requires violation of the ventricular system 3. The subject has or had any active infection requiring antibiotic, antifungal or antiviral therapy within the past 4 weeks 4. The subject has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of the scheduled surgery that cannot be stopped for surgery 5. The subject received any investigational treatment for any reason within the past 30 days. Investigational agents used to improve surgical resection or craniotomy wound healing or recovery are allowed. 6. The subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery 7. Prior intracranial gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is not allowed 8. Severe pulmonary, cardiac or other systemic disease, specifically: * New York Heart Association \> Grade 2 congestive heart failure within 6 months prior to study entry, unless asymptomatic and well controlled with medication (see Appendix G) * Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ≥ Grade 2 dyspnea, according to CTCAE 4.03) * Subjects who have any other disease, either metabolic or psychological, which as per Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications 9. The subject is breast feeding 10. The subject is HIV positive 11. The subject has a history of allergy or intolerance to flucytosine 12. The subject has a gastrointestinal disease that would prevent him or her from being able to swallow Toca FC tablets or absorb flucytosine