INTRODUCTION: Many clinical questions about brain and spinal cord tumours remain unanswered. Objectives of the Neuro-Oncology Priority Setting Partnership (PSP) were: To identify the top 10 treatment uncertainties in diagnosis and management of primary central nervous system (CNS) tumours; To highlight the necessity of a brain tumour community collaborative approach to priority setting in clinical research; To encourage other countries to use the PSP methodology to draw international comparisons. METHOD: 30 stakeholder representatives from a cross section of the UK brain tumour community were recruited. The scope was: clinical uncertainties of interventions for primary brain or spinal cord tumours. The first public survey was widely publicised by websites, MDMs, professional and charity databases. Questions were categorised and standardised into the PICO format. A Cochrane style literature search was performed to ensure these were genuine “uncertainties”. Initial prioritisation used standard James Lind Alliance (JLA) methodology. A second public survey was performed using the prioritised questions, to ask the community to rate the questions. A final workshop determined the top 10 questions using a modified Delphi and Nominal Group technique. RESULTS: Over 600 individual questions were generated from the initial survey, a patient forum and the Database of Treatment Uncertainties (DUETS). These were analysed and reduced to 44 PICO questions. These were sent out in a second public survey. The penultimate group of 25 questions was discussed at a final workshop, reaching agreement on the final top 10 uncertainties. CONCLUSION: To focus attention on what really matters to those affected by brain and spinal cord tumours, it is crucial to promote the 10 clinical research uncertainties (http://www.neuro-oncology.org.uk) to governmental, neuroscience and charity funders throughout 2015/16. This has been a very successful and rewarding joint collaboration between CNS patients/carers, major charities and multidisciplinary professional organisations.